Application of Long-acting VLHL PAI-1 During Sutureless Partial Nephrectomy in Mice Reduces Bleeding

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2015 Apr 18

PMID 25883959

Authors

Khaled Shahrour

Rick Keck

Jerzy Jankun

Affiliations

Soon will be listed here.

Abstract

PAI-1 prevents lysis of blood clot by inhibiting the urokinase and tPA induced conversion of plasminogen to plasmin. VLHL PAI-1 protein mutant was created to extend half-life over 700 hours. The objective of this paper was to test VLHL PAI-1 effects on bleeding during partial nephrectomy in mice. All animals had a left partial nephrectomy after intravenous infusion of saline or tPA. The animals were divided into four groups. Group 1 was infused with saline and kidney was exposed to saline too; Group 2 was infused with saline and kidney was exposed to PAI-1. Group 3 was infused with tPA and kidney was exposed to saline, while Group 4 was infused with tPA and kidney was exposed to PAI-1. Preweighed gauze containing PAI-1 or saline was then applied to the kidney for 30 minutes. The gauze was afterward weighed and blood loss was measured by subtracting the preweight of gauze from the final weight. We have observed a statistically significant (P ≤ 0.05) reduction of bleeding in PAI-1-treated group in comparison to saline and tPA-treated groups. Based on these results we propose that VLHL PAI-1 can be used therapeutically in limiting the flow of blood from renal wounds.

References

Berkenpas M, Lawrence D, Ginsburg D . Molecular evolution of plasminogen activator inhibitor-1 functional stability. EMBO J. 1995; 14(13):2969-77. PMC: 394356. DOI: 10.1002/j.1460-2075.1995.tb07299.x. View

TUTHILL D, Bayer V, Gallagher A, Drohan W, MacPhee M . Assessment of topical hemostats in a renal hemorrhage model in heparinized rats. J Surg Res. 2001; 95(2):126-32. DOI: 10.1006/jsre.2000.6027. View

Sugiki M, Maruyama M, Yoshida E, Mihara H, Kamiguti A, Theakston D . Enhancement of plasma fibrinolysis in vitro by jararhagin, the main haemorrhagic metalloproteinase in Bothrops jararaca venom. Toxicon. 1995; 33(12):1605-17. DOI: 10.1016/0041-0101(95)00102-6. View

Fay W, Parker A, Condrey L, Shapiro A . Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene. Blood. 1997; 90(1):204-8. View

Kohro S, Yamakage M, Omote T, Namiki A . In vitro effects of propofol on blood coagulability and fibrinolysis by the use of thromboelastograph technique. Acta Anaesthesiol Scand. 1999; 43(2):217-9. DOI: 10.1034/j.1399-6576.1999.430217.x. View

De Taeye B, Gils A, Declerck P . The story of the serpin plasminogen activator inhibitor 1: is there any need for another mutant?. Thromb Haemost. 2004; 92(5):898-924. DOI: 10.1160/TH04-05-0269. View

Xia V, Steadman R . Antifibrinolytics in orthotopic liver transplantation: current status and controversies. Liver Transpl. 2005; 11(1):10-8. DOI: 10.1002/lt.20275. View

Largent V, Deneys V, Brichard B, Chantrain C, Vermylen C . Bleeding diathesis in a child with normal screening tests: think about fibrinolysis. Eur J Pediatr. 2005; 164(9):587-8. DOI: 10.1007/s00431-005-1683-2. View

Feinbloom D, Bauer K . Assessment of hemostatic risk factors in predicting arterial thrombotic events. Arterioscler Thromb Vasc Biol. 2005; 25(10):2043-53. DOI: 10.1161/01.ATV.0000181762.31694.da. View

10.

Gallimore M, Harris S, Tappenden K, Winter M, Jones D . Urokinase induced fibrinolysis in thromboelastography: a model for studying fibrinolysis and coagulation in whole blood. J Thromb Haemost. 2005; 3(11):2506-13. DOI: 10.1111/j.1538-7836.2005.01615.x. View

11.

Smolarczyk K, Boncela J, Szymanski J, Gils A, Cierniewski C . Fibrinogen contains cryptic PAI-1 binding sites that are exposed on binding to solid surfaces or limited proteolysis. Arterioscler Thromb Vasc Biol. 2005; 25(12):2679-84. DOI: 10.1161/01.ATV.0000189305.84297.8b. View

12.

Richard B, Pichon S, Arocas V, Venisse L, Berrou E, Bryckaert M . The serpin protease nexin-1 regulates vascular smooth muscle cell adhesion, spreading, migration and response to thrombin. J Thromb Haemost. 2006; 4(2):322-8. DOI: 10.1111/j.1538-7836.2006.01710.x. View

13.

Jankun J, Aleem A, Specht Z, Keck R, Lysiak-Szydlowska W, Selman S . PAI-1 induces cell detachment, downregulates nucleophosmin (B23) and fortilin (TCTP) in LnCAP prostate cancer cells. Int J Mol Med. 2007; 20(1):11-20. View

14.

Minowa H, Takahashi Y, Tanaka T, Naganuma K, Ida S, MAKI I . Four cases of bleeding diathesis in children due to congenital plasminogen activator inhibitor-1 deficiency. Haemostasis. 2000; 29(5):286-91. DOI: 10.1159/000022514. View

15.

Westrick R, Eitzman D . Plasminogen activator inhibitor-1 in vascular thrombosis. Curr Drug Targets. 2007; 8(9):966-1002. DOI: 10.2174/138945007781662328. View

16.

Jankun J, Aleem A, Selman S, Skrzypczak-Jankun E, Lysiak-Szydlowska W, Grafos N . Highly stable plasminogen activator inhibitor type one (VLHL PAI-1) protects fibrin clots from tissue plasminogen activator-mediated fibrinolysis. Int J Mol Med. 2007; 20(5):683-7. View

17.

Taneda S, Hudkins K, Muhlfeld A, Kowalewska J, Pippin J, Shankland S . Protease nexin-1, tPA, and PAI-1 are upregulated in cryoglobulinemic membranoproliferative glomerulonephritis. J Am Soc Nephrol. 2008; 19(2):243-51. PMC: 2396743. DOI: 10.1681/ASN.2007030367. View

18.

Schneeweiss S, Seeger J, Landon J, Walker A . Aprotinin during coronary-artery bypass grafting and risk of death. N Engl J Med. 2008; 358(8):771-83. DOI: 10.1056/NEJMoa0707571. View

19.

Evans P, Hawkins K, Lawrence M, Barrow M, Williams P, Williams R . Studies of whole blood coagulation by oscillatory shear, thromboelastography and free oscillation rheometry. Clin Hemorheol Microcirc. 2008; 38(4):267-77. View

20.

Carroll R, Craft R, Chavez J, Snider C, Kirby R, Cohen E . Measurement of functional fibrinogen levels using the Thrombelastograph. J Clin Anesth. 2008; 20(3):186-90. DOI: 10.1016/j.jclinane.2007.09.017. View